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  • Short- and long-term effects of antipsychotic drug treatment on weight gain and H1 receptor expression

    Author(s)
    Han, Mei
    Deng, Chao
    Burne, Thomas HJ
    Newell, Kelly A
    Huang, Xu-Feng
    Griffith University Author(s)
    Burne, Thomas HJ.
    Year published
    2008
    Metadata
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    Abstract
    The present study investigated body weight gain, food intake, open-field activity and brain histamine H1 receptor mRNA and protein expression in rats treated with three types of antipsychotics. Rats were divided into eight groups and treated with aripiprazole (2.25 mg/kg/day), olanzapine (1.5 mg/kg/day), haloperidol (0.3 mg/kg/day) or vehicle (as control) for 1 or 12 weeks. Administration of olanzapine for 1 week led to a threefold increase in body weight gain and a 35% increase in fat deposits compared to controls (p<0.05). In the 12-week olanzapine treatment group, accumulative food intake was significantly higher in the ...
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    The present study investigated body weight gain, food intake, open-field activity and brain histamine H1 receptor mRNA and protein expression in rats treated with three types of antipsychotics. Rats were divided into eight groups and treated with aripiprazole (2.25 mg/kg/day), olanzapine (1.5 mg/kg/day), haloperidol (0.3 mg/kg/day) or vehicle (as control) for 1 or 12 weeks. Administration of olanzapine for 1 week led to a threefold increase in body weight gain and a 35% increase in fat deposits compared to controls (p<0.05). In the 12-week olanzapine treatment group, accumulative food intake was significantly higher in the first 7 weeks of treatment compared to controls (p<0.018), while body weight gain was significantly greater in the first 8 weeks compared to controls (p<0.045). Using in situ hybridization, we found that olanzapine treatment, but not aripiprazole or haloperidol treatment, significantly reduced H1 receptor mRNA expression in the arcuate hypothalamic nucleus (Arc: -18%, p=0.006, 1 week; -20%, p=0.008, 12 weeks) and ventromedial hypothalamic nucleus (VMH: -22%, p=0.006, 1 week; -19%, p=0.042, 12 weeks) compared to controls. The quantitative autoradiography data showed a reduction in VMH H1 receptor binding density after 1 (-12%, p=0.040) and 12 (-10%, p=0.094) weeks of olanzapine treatment. There were significant negative correlations between the levels of H1 receptor mRNA expression, and body weight gain and energy efficiency in the Arc and VMH after 1- and 12-week antipsychotic treatments in all groups. In addition, H1 receptor mRNA expression in the Arc showed a significant negative correlation with food intake and fat mass in all groups. Furthermore, there were negative correlations between H1 receptor binding density in the VMH and total fat mass and body weight gain after 1 week of antipsychotic treatment. The present study suggests that downregulated VMH and Arc H1 receptor expression may be a key factor contributing to olanzapine-induced obesity.
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    Journal Title
    Psychoneuroendocrinology
    Volume
    33
    Issue
    5
    DOI
    https://doi.org/10.1016/j.psyneuen.2008.01.018
    Subject
    Medicinal and biomolecular chemistry not elsewhere classified
    Biomedical and clinical sciences
    Psychology
    Publication URI
    http://hdl.handle.net/10072/23276
    Collection
    • Journal articles

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